Ductus arteriosus is a normal connecting blood vessel between the pulmonary artery and aorta in the fetus. However, if the ductus arteriosus is not closed and maintained as the open state even after 72 h of the birth, this is called a patent ductus arteriosus (PDA). Intravenous indomethacin is the conventional treatment for PDA in immature infants, but remains controversial in mature infants. The purpose of this study was to compare intravenous indomethacin and oral ibuprofen with regard to efficacy and safety for treatment of PDA. 78 neonates treated for PDA were included and classified into immature (n = 49) and mature (n = 29) groups. Ductal closure occurred in immature infants treated with indomethacin (74.1%) and ibuprofen (90.9%). Ductal closure occurred in mature infants treated with indomethacin (66.7%) and ibuprofen (92.9%). Platelet counts were increased in immature infants treated with ibuprofen (p = 0.027). Hyponatremia occurred in immature infants treated with ibuprofen (p = 0.002) and in both groups of mature infants (p = 0.001 for both groups). Serum creatinine values were lowered in mature infants treated with ibuprofen (p = 0.032). Bleeding occurred in 5 immature infants treated with indomethacin. Administration of furosemide for urine output was more frequent in the mature groups than in the immature group. In conclusion, oral ibuprofen was as effective as intravenous indomethacin in the immature groups and more effective in the mature groups. Adverse effects of oral ibuprofen were less severe than intravenous indomethacin.